The words of the body: psychophysiological patterns in dissociative narratives

Trauma has severe consequences on both psychological and somatic levels, even affecting the genetic expression and the cell\u2019s DNA repair ability. A key mechanism in the understanding of clinical disorders deriving from trauma is identified in dissociation, as a primitive defense against the fragmentation of the self originated by overwhelming experiences. The dysregulation of the interpersonal patterns due to the traumatic experience and its detrimental effects on the body are supported by influent neuroscientific models such as Damasio\u2019s somatic markers and Porges\u2019 polyvagal theory. On the basis of these premises, and supported by our previous empirical observations on 40 simulated clinical sessions, we will discuss the longitudinal process of a brief psychodynamic psychotherapy (16 sessions, weekly frequency) with a patient who suffered a relational trauma. The research design consists of the collection of self-report and projective tests, pre-post therapy and after each clinical session, in order to assess personality, empathy, clinical alliance and clinical progress, along with the verbatim analysis of the transcripts trough the Psychotherapy Process Q-Set and the Collaborative Interactions Scale. Furthermore, we collected simultaneous psychophysiological measures of the therapeutic dyad: skin conductance and hearth rate. Lastly, we employed a computerized analysis of non-verbal behaviors to assess synchrony in posture and gestures. These automated measures are able to highlight moments of affective concordance and discordance, allowing for a deep understanding of the mutual regulations between the patient and the therapist. Preliminary results showed that psychophysiological changes in dyadic synchrony, observed in body movements, skin conductance and hearth rate, occurred within sessions during the discussion of traumatic experiences, with levels of attunement that changed in both therapist and the patient depending on the quality of the emotional representation of the experience. These results go in the direction of understanding the relational process in trauma therapy, using an integrative language in which both clinical and neurophysiological knowledge may take advantage of each other

PO-035 LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitor

Introduction Lung Cancer is the first cause of cancer-related death in the world. The alterations in KRAS oncogene are very frequent (25%), but, unfortunately, this protein is at present undruggable. KRAS mutations determine over-activation of important pathways of growth and proliferation (PI3K-AKT-mTOR and MAPK). KRAS-mutated tumours are also frequently co-mutated in LKB1 (50%), an important regulator of metabolic homeostasis and oxidative stress in the cells. LKB1 modulates catabolic processes through AMPK-mediated mTOR inhibition. Thereafter, the inactivation of LKB1 causes in KRAS mutated-tumours further activation of PI3K-AKT-mTOR and MAPK pathways, making them particularly aggressive. The possibility to specifically target tumours with both KRAS and LKB1 alterations represent an important medical need. Material and methods We generated from the NSCLC cell line NCI-H1299 clones over-expressing KRAS WT or KRAS G12C forms. These clones have been subsequently modified through CRISPR-CAS9 system to obtain deletions in LKB1 gene. We successfully generated isogenic cells differing only for the status of KRAS and LKB1 (KRASwt/LKB1wt, KRASmut/LKB1wt, KRASwt/LKB1mut, KRASmut/LKB1mut). These clones were treated with a panel of inhibitors of MAPK and PI3K pathways. Viability was evaluated with MTS assay. Molecular characterizations were performed by western blot analysis. In vivo antitumor activity was determined after subcutaneous injection of NSCLC cells in immunodeficient mice. Results and discussions Using the isogenic system generated we tested the activity of several inhibitors of MAPK and PI3K pathways. The results highlighted a strong response of the clones with deletion in LKB1 to ERK inhibitor, independently from the KRAS status. These results were confirmed 'in vivo', where tumours with LKB1 deletion showed a significant sensitivity to ERK inhibitor, compared to LKB1 WT tumours. At molecular level we tested the activation of proteins related to MAPK and PI3K pathway such as p70, S6, 4-EBP1, ERK. The results showed that the response to ERK inhibitor was mainly due to mTOR signalling inhibition. Conclusion The results obtained highlight a possible strategy to target NSCLC with KRAS-LKB1 co-mutations, that, at moment are those with a worse prognosis. The sensitivity to ERK inhibitor is remarkable, also in presence of KRAS WT, therefore this strategy could be applied to all LKB1-mutated lung tumours, that represent 30% of all NSCLC. These studies are being confirmed in other NSCLC backgrounds and mouse models

A Corpus for Sentence-level Subjectivity Detection on English News Articles

We present a novel corpus for subjectivity detection at the sentence level. We develop new annotation guidelines for the task, which are not limited to language-specific cues, and apply them to produce a new corpus in English. The corpus consists of 411 subjective and 638 objective sentences extracted from ongoing coverage of political affairs from online news outlets. This new resource paves the way for the development of models for subjectivity detection in English and across other languages, without relying on language-specific tools like lexicons or machine translation. We evaluate state-of-the-art multilingual transformer-based models on the task, both in mono- and cross-lingual settings, the latter with a similar existing corpus in Italian language. We observe that enriching our corpus with resources in other languages improves the results on the task

Outcomes and indications for Emergency Thoracotomy after adoption of a more liberal policy in a western European level 1 Trauma Center: 8-years experience.

Background: The role of Emergency Thoracotomy (ET) in blunt trauma is still a matter of debate and in Europe only small studies have been published. We report our experience about ET both in penetrating and blunt trauma, discussing indications, outcomes and proposing an algorithm for patient selection. Materials and methods: We retrospectively analysed patients who underwent ET at Maggiore Hospital Trauma Center over two periods: from January 1st, 2010 to December 31st, 2012, and from January 1st, 2013 to May 31st, 2017. Demographic and clinical data, mechanism of injury, Injury Severity Score, site of injury, time of witnessed cardiac arrest, presence/absence of signs of life, length of stay, were considered, as well as survival rate and neurological outcome. Results: 27 ETs were performed; 21 after blunt trauma and six after penetrating trauma. Motor vehicle accident was the main mechanism of injury, followed by fall from height. The mean age was 40,5 years and the median Injury Severity Score was of 40. The most frequent injury was cardiac tamponade. The overall survival rate was 10% during the first period and 23.5% during the second period, after the adoption of a more liberal policy. No long term neurological sequelae were reported. Conclusions: The outcomes of ET in trauma patient, either after penetrating or blunt trauma, are poor but not negligible. To date, only small series of ET from European trauma centers have been published, although larger series are available from USA and South Africa. However, in selected patients, all efforts must be made for the patient's survival; the possibility of organ donation should be taken into consideration as well

Applications of Robotics for Autism Spectrum Disorder: a Scoping Review

Robotic therapies are receiving growing interest in the autism field, especially for the improvement of social skills of children, enhancing traditional human interventions. In this work, we conduct a scoping review of the literature in robotics for autism, providing the largest review on this field from the last five years. Our work underlines the need to better characterize participants and to increase the sample size. It is also important to develop homogeneous training protocols to analyse and compare the results. Nevertheless, 7 out of the 10 Randomized control trials reported a significant impact of robotic therapy. Overall, robot autonomy, adaptability and personalization as well as more standardized outcome measures were pointed as the most critical issues to address in future research

Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) Patients: A Retrospective Analysis of Eligibility Criteria for CAR-T Cell Therapy

Patients (pts) with diffuse large B-cell lymphoma (DLBCL) refractory to second-line therapy or relapsed after an autologous stem cell transplant (ASCT) have a very poor clinical outcome with a median overall survival (OS) of 5 and 8-10 months, respectively. Autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T cells have been associated with sustained complete remissions and long-term survivals in a large proportion of pts with R/R DLBCL by the two pivotal clinical trials Zuma1 and Juliet. This has led to the rapid approval by FDA and then by EMA of CAR-T cells for the third-line treatment of R/R DLBCL. Despite being a potentially revolutionary treatment for pts with advanced disease, the costs are much greater than any previously approved cancer therapy and this may become a substantial economic challenge for the health care system. The definition of inclusion and exclusion criteria capable of identifying more precisely pts who can successfully undergo CAR-T cell therapy, minimizing the severity of the toxicity, still remains a matter of discussion. Moreover, some eligible pts run the risk of becoming ineligible because of poor disease control. Indeed, one of the major obstacles to the successful use of CAR-T cells is the 4-5 week period so far required for the manufacturing and transfer of CAR-T cells. To address this issue, we have examined data of R/R DLBCL pts managed between 2010 and 2018 at our Center in order to: 1) better identify the characteristics and outcome of a cohort of R/R DLBCL pts potentially eligible, according to the approval criteria, for CAR-T cell therapy; 2) define factors influencing CAR-T cell eligibility; 3) make a realistic estimate of pts eligible for CAR-T cells. In this retrospective real-life cohort of R/R DLBCLs, 82/480 pts (17%) were R/R tosecond-line treatment including ASCT. Considering Juliet's inclusion/exclusion criteria for CAR-T cell therapy, only 50 pts (10.4%) would be eligible for CAR-T cells. Our analysis suggests that elevated LDH plus ECOG ≥2 have to be considered the two most significant features of very rapid disease progression. These variables should be taken in account in order to better select DLBCL pts potentially eligible to CAR-T therapy

Genome-wide characterisation and expression profile of the grapevine ATL ubiquitin ligase family reveal biotic and abiotic stress-responsive and development-related members

The Arabidopsis T\uf3xicos en Levadura (ATL) protein family is a class of E3 ubiquitin ligases with a characteristic RING-H2 Zn-finger structure that mediates diverse physiological processes and stress responses in plants. We carried out a genome-wide survey of grapevine (Vitis vinifera L.) ATL genes and retrieved 96 sequences containing the canonical ATL RING-H2 domain. We analysed their genomic organisation, gene structure and evolution, protein domains and phylogenetic relationships. Clustering revealed several clades, as already reported in Arabidopsis thaliana and rice (Oryza sativa), with an expanded subgroup of grapevine-specific genes. Most of the grapevine ATL genes lacked introns and were scattered among the 19 chromosomes, with a high level of duplication retention. Expression profiling revealed that some ATL genes are expressed specifically during early or late development and may participate in the juvenile to mature plant transition, whereas others may play a role in pathogen and/or abiotic stress responses, making them key candidates for further functional analysis. Our data offer the first genome-wide overview and annotation of the grapevine ATL family, and provide a basis for investigating the roles of specific family members in grapevine physiology and stress responses, as well as potential biotechnological applications